Role of cell-cycle inhibitor p21 in cardiac hypertrophy

细胞周期抑制剂 p21 在心脏肥大中的作用

• 批准号: 15590769
• 负责人: YAMAMOTO Keiji
• 金额: $ 2.11万
• 依托单位: JICHI MEDICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590769/
• 关键词: cardiac hypertrophy; cell cycle; mouse; heart failure; pressure overload; )細胞周期; )圧負荷

Pressure overload conditions such as hypertension are clinically important. Cardiomyocytes undergo terminal differentiation soon after birth, irreversibly withdrawing from the cell cycle. Previous studies from other groups have determined that cardiomyocytes expressed some of cell-cycle regulators and that cdk activity may be required for the induction of cardiomyocyte hypertrophy. Nonetheless, the exact roles and significance of these regulators in cardiomyocytes are still not precisely understood. In this study, we clarified the role of cell-cycle inhibitor p21, one of cyclin-dependent kinase inhibitors, in cardiac hypertrophy. First, we generated α-myosin heavy chain cardiac-specific p21-expreesing transgenic (p21Tg) mice. In Western blot analysis, two lines of p21Tg mice were obtained. In p21Tg mice, left ventricle was more hypertrophic compared with that of wild-type mice. Next, a model of cardiac hypertrophy was made by abdominal aortic banding as follows. A laparotomy was performed. The aortic aorta was isolated from annexed tissue, and the artery was partially ligated immediately below the celiac trunk with 7-0 silk around a 27-gauge blunted needle. Using echocardiography, cardiac ventricular dimensions and wall thicknesses were measured on 2-dimensional M-mode images at least 3 times foe each animal. In wild-type mice, wall thickness of left ventricle was increased 16 weeks after abdominal aortic banding. However, in p21Tg mice, left ventricle was dilated and its wall thickness was thin 16 weeks after abdominal aortic banding. These findings provide further evidence implicating cell-cycle factors as obligate regulators of cardiac hypertrophy and suggest that p21 may play an important role in non-compensated conditions for chronic pressure overload in heart.

高血压在临床上很重要。细胞周期抑制剂p21，一种依赖细胞周期的激酶抑制剂，首先是α-肌球蛋白重的心脏特异性P21的转基因（P21TG）。与野生型小鼠相比，肥大性的腹部主动脉束缚和动脉的腹部主动脉均匀在野生型小鼠中，每只动物的敌人至少3倍，腹部主动脉束缚后16周增加隐含因素是心脏肥大的强制调节因子，并表明p21在心脏中慢性压力超负荷的非补偿条件中可能起重要作用。

项目成果

Yamamoto K: "Role of mechanical stress in monocytes/macrophages : implications for atherosclerosis."Current Vascular Pharmacology. 1. 315-319 (2003)

Yamamoto K：“机械应力在单核细胞/巨噬细胞中的作用：对动脉粥样硬化的影响。”当前血管药理学。

Gene expression profiling of human atrial myocardium with atrial fibrillation by DNA microarray analysis

• DOI: 10.1016/j.ijcard.2004.05.026
• 发表时间: 2005-07-10
• 期刊: INTERNATIONAL JOURNAL OF CARDIOLOGY
• 影响因子: 3.5
• 作者: Ohki, R;Yamamoto, K;Shimada, K
• 通讯作者: Shimada, K

Ohki R: "Effects of olmesartan, an angiotensin II receptor blocker, on mechanic ally-modulated genes in cardiac myocytes."Cardiovasc Drugs Ther. 17. 231-236 (2003)

Ohki R：“奥美沙坦（一种血管紧张素 II 受体阻滞剂）对心肌细胞中机械调节基因的影响。”Cardiovasc Drugs Ther。

Transcriptional profile of genes induced in human atrial myocardium with pressure overload.

人心房心肌压力超负荷诱导的基因转录谱。

• 发表时间: 2004
• 期刊: Int J Cardiol 96
• 作者: Yamamoto K;et al.;Ohki R
• 通讯作者: Ohki R

Nonaka-Sarukawa M: "Increased urinary 15-F_<2t>-isoprostane concentrations in patients with non-ischaemic congestive heart failure : a marker of oxidative stress."Heart. 89. 871-874 (2003)

Nonaka-Sarukawa M：“非缺血性充血性心力衰竭患者尿中 15-F_2t>-异前列腺素浓度增加：氧化应激的标志。”心脏。